Promoter Elements Regulate Cytoplasmic mRNA Decay

Bregman, Almog; Avraham-Kelbert, Moran; Barkai, Oren; Duek, Lea; Guterman, Adi; Choder, Mordechai

doi:10.1016/j.cell.2011.12.005

Cited by 174 publications

(188 citation statements)

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“…They may include 3′ end formation and coupled polyadenylation, splicing, mRNA export as well as cytoplasmic events involving translation, RNA binding proteins (RBP) and miRNAs (Joshi et al, 2012). Interestingly, a few recent reports highlight the tight coupling between transcriptional regulation and post-transcriptional events that govern mRNA stability (Bregman et al, 2011; Trcek et al, 2011). In these examples, RBPs are recruited by specific transcription factors, which then help load the RBPs onto nascent RNA; they then control cytoplasmic mRNA stability (Bregman et al, 2011; Trcek et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a few recent reports highlight the tight coupling between transcriptional regulation and post-transcriptional events that govern mRNA stability (Bregman et al, 2011; Trcek et al, 2011). In these examples, RBPs are recruited by specific transcription factors, which then help load the RBPs onto nascent RNA; they then control cytoplasmic mRNA stability (Bregman et al, 2011; Trcek et al, 2011). A mechanism of this nature could account for the post-transcriptional generation of rhythmic mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

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Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Menet

Rodriguez

Abruzzi

et al. 2012

eLife

295

405

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A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues. Based on the transcription feedback loops important for circadian timekeeping, it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation. To address this issue, we directly measured the circadian dynamics of mouse liver transcription using Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional rhythms, indicating a prominent contribution of post-transcriptional regulation to circadian mRNA expression. This analysis of rhythmic transcription also showed that the rhythmic DNA binding profile of the transcription factors CLOCK and BMAL1 does not determine the transcriptional phase of most target genes. This likely reflects gene-specific collaborations of CLK:BMAL1 with other transcription factors. These insights from Nascent-Seq indicate that it should have broad applicability to many other gene expression regulatory issues.DOI: http://dx.doi.org/10.7554/eLife.00011.001

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Menet

Rodriguez

Abruzzi

et al. 2012

eLife

295

405

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“…Although the present demonstration that mammalian TFs can actively participate in the process of cytoplasmic mRNA degradation was highly unexpected, our work comes in the wake of recent genetic and molecular evidence establishing functional coupling between mRNA synthesis and degradation in yeast [42][43][44] . In particular, specific promoter sequences in yeast have been shown to influence cytoplasmic mRNA decay, presumably through their associated TFs 12,13 .…”

Section: Discussionmentioning

confidence: 99%

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

Rambout

Detiffe

Bruyr

et al. 2016

Nat Struct Mol Biol

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nature structural & molecular biology advance online publication a r t i c l e sAlthough undisputable evidence has clearly demonstrated that the nuclear steps of mRNA processing are mechanistically linked to transcription, a conceptual evolution in gene regulation has come with the realization that transcription might also be functionally connected to more remote processes occurring in the cytoplasm, such as mRNA decay 1,2 . Cytoplasmic mRNA decay is initiated by deadenylation, a rate-limiting event during which the poly(A) tail of the transcript is trimmed off by the CCR4-NOT complex, the main deadenylation machinery in eukaryotes 3 . The degradation of specific mRNAs, a key process in the regulation of eukaryotic gene expression, is achieved through the recruitment of the CCR4-NOT complex by sequence-specific RNA-binding proteins (RBPs) or by the microRNA machinery 3,4 . Poly(A)-shortened mRNAs, along with factors involved in the deadenylation, decapping and mRNA-degradation machineries, accumulate in microscopic mRNA-protein complex (mRNP) aggregates called processing bodies (PBs) 5 .The idea of coupling between mRNA synthesis and degradation has recently emerged. Genome-wide expression studies in yeast have shown that mRNA synthesis and decay are mechanistically and functionally coordinated, thus supporting the existence of common molecular effectors [6][7][8][9] . In particular, the CCR4-NOT deadenylation complex was first described as a transcriptional regulator and has been implicated in initiation and elongation by RNA polymerase II 10,11 . More surprisingly, it has also been shown that degradation of yeast mRNAs is determined by cis-acting sequence elements in promoters 12,13 . These findings have led to the concept of mRNA imprinting, in which sequence-specific DNA-binding factors might orchestrate mRNA synthesis and decay. This decay would occur via loading of factors regulating cytoplasmic mRNA degradation onto the transcribing mRNA 14 . However, the identity of these DNA-binding mRNA coordinators is still obscure, and it remains to be tested whether such coupling between transcription and decay also exists in higher eukaryotes. E26 (Ets) proteins, a family of 28 helix-loop-helix transcription factors (TFs) in metazoans, are characterized by a highly conserved DNA-binding ETS domain 15 . Through this domain, Ets factors bind specific gene promoters and act as key regulators in many biological processes including cellular proliferation, apoptosis, differentiation and survival 16 . ERG, FLI1 and the more structurally divergent FEV compose the Erg subfamily of Ets factors and have been identified as driving factors in prostate cancer, Ewing's tumors and leukemias 15,17 . Using ERG as a paradigm, we sought to investigate the possibility that eukaryotic transcription factors might be directly involved in cytoplasmic mRNA decay. We demonstrate that ERG triggers degradation of mRNAs connected to Aurora signaling by recruiting RBPs and the CCR4-NOT deadenylation complex and that this activity is important fo...

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“…Recent studies in yeast and humans indicated that these processes are interconnected and that cis-acting sequences help to coordinate transcription and mRNA decay (Goler-Baron et al 2008;Bregman et al 2011). Moreover, these data implied that TFs regulate distinct processes of gene expression by interacting with multiple cofactors dedicated to individual steps in gene expression and/or with protein complexes that harbor multiple functional activities.…”

Section: Discussionmentioning

confidence: 99%

Interaction of CCR4–NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis

et al. 2016

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Transcription factor EBF1 (early B-cell factor 1) regulates early B-cell differentiation by poising or activating lineagespecific genes and repressing genes associated with alternative cell fates. To identify proteins that regulate the diverse functions of EBF1, we used SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry of proteins associated with endogenous EBF1 in pro-B cells. This analysis identified most components of the multifunctional CCR4-NOT complex, which regulates transcription and mRNA degradation. CNOT3 interacts with EBF1, and we identified histidine 240 in EBF1 as a critical residue for this interaction. Complementation of Ebf1 −/− progenitors with EBF1H240A revealed a partial block of pro-B-cell differentiation and altered expression of specific EBF1 target genes that show either reduced transcription or increased mRNA stability. Most deregulated EBF1 target genes show normal occupancy by EBF1H240A, but we also detected genes with altered occupancy, suggesting that the CCR4-NOT complex affects multiple activities of EBF1. Mice with conditional Cnot3 inactivation recapitulate the block of early B-cell differentiation, which we found to be associated with an impaired autoregulation of Ebf1 and reduced expression of pre-B-cell receptor components. Thus, the interaction of the CCR4-NOT complex with EBF1 diversifies the function of EBF1 in a context-dependent manner and may coordinate transcriptional and post-transcriptional gene regulation.

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Promoter Elements Regulate Cytoplasmic mRNA Decay

Cited by 174 publications

References 50 publications

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

Interaction of CCR4–NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis

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